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Description of key information

No data were located for N,N-dimethylbutylamine (DMBA). Therefore, cross reading from data on n-Butanol, n-Butylacetate  und dimethylamine was made, for RAC justification please refer to section 7.1.
Dimethylamine
No specific data for oral repeated dose toxicity
No data for dermal repeated dose dixicity
For inhalation repeated dose toxicity only available in ppm, see Buckley (1985)
n-Butanol
oral
rat, 90d: NOAEL = 125 mg/kg bw (based on CNS effects; US EPA 1986)

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

No data were located for N,N-dimethylbutylamine (DMBA). Therefore, cross reading from data on reltd substances :n-Butanol, n-Butylacetate und dimethylamine was made, for RAC justification please refer to section 7.1.

Dimethylamine

Inhalation:

Rats (95 Fischer 344/sex and dose) and mice were exposed to atmospheres containing dimethylamine at 0, 10, 50, 175 ppm (exposure duration 12 months, 5 days/week, 6 hours/day). The concentration was monitored using IR spectrophotometry. Groups of rats (and mice) were sacrificed at 6 and 12 months after study initiation. Examinations included clinical signs body weights, clinical chemistry, haematology, necropsy and histopathology.After 12 months of exposure, the only effect noted was a dose-dependent irritation of the nasal respiratory and olfactory epithelium, both in rats and mice, without any gender or species related differences. At 10 ppm the effects were minimal but present in several animals. Deaths occurred at 175 ppm in high incidence in male mice (Buckley et al, 1985). The results indicate that the mode of action of the free amine is local irritation/corrosion at the point of contact, followed by inflammatory processes with concomitant alterations of the blood cell counts. Systemic toxicity is a minor issue and there was no indication in this study for any kind of systemic toxicity or target organ other than the airways. This result is in line with observations made with other saturated aliphatic amines. Therefore, the result can be read across to related substances, including N,N-dimethylamine, and can be used for assessment.. In this study the LOAEC for local effects was 10 ppm DMA (= 18.7 mg/m³), the NOAEC for systemic toxicity was 50 ppm DMA (93.5 mg/m³).

n-Butanol:

Valid experimental data to assess systemic toxicity after repeated dosage were available only for the oral pathway. For the dermal and inhalative pathway, available data are very limited. Therefore, for the inhalative route, reliable data were taken from the analogous substance n-Butyl acetate (CAS-No. 123-86-4).

Oral

Four groups of male and female Sprague-Dawley rats (30/sex/group) were administered daily 0, 30, 125 or 500 mg/kgbw/d by gavage for either 6 or 13 weeks (US EPA 1986). No dose-related differences were observed between treatment or control rats in body or organ weight changes, food consumption or mortality, gross pathology, and histopathological and ophthalmic evaluations. CNS effects seen as transient clinical signs (ataxia and hypoactivity, lasting less than 1 h after dosing; a typical effect of alcohols) were found at the 500 mg/kg bw animals, therefore the NOAEL of 125 mg/kg bw is considered. These effects were seen only in the second part of the study period as animal number was reduced and post-dose observations were performed more quickly.

 

Dermal

Butan-1-ol was applied to rabbit skin under occlusive conditions for 12* 5 h within 21 d (Omie et al. 1949). Drying of the skin was reported and on continuous exposure, cracking, furrowing and exfoliation of the epidermis. No systemic effects were noted without information of the scope of survey.

 

Inhalation

Subchronic effects of butan-1-ol were studied in 12 males Wistar rates each exposed to 0.15 or 0.31 mg/L vapour for 6h/d and 5d/wk (Korsak et al. 1994; Val. 3). Relevant elements of a standard study for repeated exposure, including histopathological evaluation of tissues, were missing. Subsequently, no local effects could be detected in this inhalation study and therefore no assessment can be made from this study. A LOEL of 0.15 mg/L based on effects on hematology and clinical chemistry can be determined. A decreased performance on the rotarod was observed at both concentrations and was considered as dose-related; however, the data were only reported in graphical form.

N-Butylacetate

Male and female Sprague-Dawley rats (15 animals/sex/dose group) were exposed to nominal concentrations of 0, 500 (increased to nominal 550 ppm), 1500 or 3000 ppm of n-butyl acetate for 6 hours per day, 5 days per week for 13 consecutive weeks. The time-weighted average analytical concentrations were within 10% of the target concentrations. Transient signs of sedation were observed during exposure to the 1500 and 3000 ppm concentrations. Body weights were significantly reduced in the mid and high concentration groups. Feed consumption was significantly lower in the 1500 and 3000 ppm group in comparison to the control group. Organ weights affected: weights of liver, kidneys and spleen were significantly lower for the males of the highest concentration group. Testes and adrenal gland weights for the mid and high concentration groups and the lung weights for the 3000 ppm males were significantly higher than for the control group. Additionally, effects on the stomach (probably stress related) and pulmonary system were observed: Females of the highest concentration group showed signs of irritation of the glandular stomach and necrosis in the non-glandular stomach. Some rats of the 1500 and 3000 ppm group showed degeneration of the olfactory epithelium along the dorsal medial meatus and ectomturbinates of the nasal passages. The severity was mild to moderate for the 3000 ppm group and minimal to mild for the 1500 ppm group. There was no systemic, organ specific toxicity. The no-observed-adverse-effect concentration (NOAEC) for this study is 2.6 mg/L (Bernard and David, 1996; David et al., 2001). Taking molecular weights into consideration this corresponds to 1.65 mg butanol/L, or 1655 mg butanol/m³. The study is considered to be reliable without restriction and supportive for the assessment of N,N-dimethylbutylamine (DMBA) because butanol is rapidly liberated in vivo from butylacetate, and butanol is also a potential metabolite of DMBA.




Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Read across to related substance

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
Read across to potential metabolite

Justification for selection of repeated dose toxicity inhalation - local effects endpoint:
Read across to potential metabolite

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:
N,N-dimethylbutylamine is corrosive to the skin

Justification for selection of repeated dose toxicity dermal - local effects endpoint:
N,N-dimethylbutylamine is corrosive to the skin

Justification for classification or non-classification

No classification proposed, in accordance with ECHA (2012), Guidance on the application of theCLP criteria, section 3.9.2.5.1.